In the manufacture of pharmaceutical preparations, an active substance is in many cases mixed with an inactive substance to achieve a sufficient volume of the pharmaceutical preparation and to obtain suitable properties of the pharmaceutical preparation. The substances frequently have the form of powder consisting of a variety of particles. Moreover, it is normally large volumes of powder that are mixed to manufacture a large number of doses of the pharmaceutical preparation. It is then most important for the mixture to be homogeneous so that the concentration of the active substance is the same in all doses, for instance in all tablets, that are manufactured from the mixture.
There is today a tendency towards the active substance being more and more potent, and consequently a smaller and smaller volume of active substance need be added to the inactive substance in mixing. This makes it more difficult to provide a homogeneous mixture. It is also difficult to preserve the homogeneity in the mixtures since pulverulent mixtures tend to form layers.
A further difficulty associated with the homogeneity arises in the manufacture of divisible tablets. Some tablets are formed with a notch indicating that these tablets may be divided to allow the user to take half a dose of the pharmaceutical preparation. For such tablets, the manufacturer must be able to guarantee that the concentration of the active substance is the desired one not only in the tablet in its entirety but also in each half of the tablet.
The homogeneity in a powder mixture can be monitored by sampling the mixture at different points of time. If the concentration of the active substance is the desired in each sample, it is assumed that the mixture is homogeneous and that the concentration in all manufactured doses is correct. Correspondingly, when manufacturing tablets, random sampling of tablets from the manufacturing line is made and the concentration is determined. If the concentration is correct, it is assumed that all tablets have the correct concentration. The concentration of the active substance in powders and tablets is in many cases determined by a wet-chemical or dry-chemical method.
An alternative method of determining the homogeneity in tablets is disclosed in U.S. Pat. No. 5,504,332. According to this patent, a NIR reflection spectrum for a pharmaceutical tablet is generated, the homogeneity of which is to be determined. This spectrum is then compared with an index (recognition index) which has been determined on the basis of spectra of previously analyzed, acceptable tablets to determine whether the homogeneity of the tablet in question is acceptable.
A drawback of this method is that it is slow since it is necessary to generate an entire spectrum for each tablet. Further it is not possible to determine how the active substance is distributed in the tablet. Nor can the method be used to study particles of the size that exists in powders.
Also in other fields in industry, there is a need to monitor the homogeneity in mixtures by measuring the concentration of a component in the mixture.